Familial Immune Thrombocytopenia Associated With a Novel Variant in IKZF1

被引：15

作者：

Sriaroon, Panida ^{[1
]}

Chang, Yenhui ^{[2
]}

Ujhazi, Boglarka ^{[1
]}

Csomos, Krisztian ^{[1
]}

Joshi, Hemant R. ^{[3
]}

Zhou, Qin ^{[3
]}

Close, Devin W. ^{[4
]}

Walter, Jolan E. ^{[1
,5
]}

Kumanovics, Attila ^{[3
,4
,6
]}

机构：

[1] Univ S Florida, Morsani Coll Med, Dept Pediat, Div Allergy Immunol & Rheumatol, St Petersburg, FL 33612 USA

[2] Johns Hopkins All Childrens Hosp, Pathol & Lab Med, St Petersburg, FL USA

[3] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA

[4] Inst Clin & Expt Pathol, ARUP Labs, Salt Lake City, UT 84108 USA

[5] Massachusetts Gen Hosp Children, Div Allergy Immunol, Boston, MA USA

[6] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA

来源：

FRONTIERS IN PEDIATRICS | 2019年 / 7卷

基金：

美国国家卫生研究院;

关键词：

primary immunodeficiency; autoimmunity; immune thrombocytopenia; ITP; IKAROS deficiency; IKZF1; B-CELLS; IKAROS;

D O I：

10.3389/fped.2019.00139

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

We report a novel variant in IKZF1 associated with IKAROS haploinsufficiency in a patient with familial immune thrombocytopenia (ITP). IKAROS, encoded by the IKZF1 gene, is a hematopoietic zinc-finger transcription factor that can directly bind to DNA. We show that the identified IKZF1 variant (p.His195Arg) alters a completely conserved histidine residue required for the folding of the third zinc-finger of IKAROS protein, leading to a loss of characteristic immunofluorescence nuclear staining pattern. In our case, genetic testing was essential for the diagnosis of IKAROS haploinsufficiency, of which known presentations include infections, aberrant hematopoiesis, leukemia, and age-related decrease in humoral immunity. Our family study underscores that, after infections, ITP is the second most common clinical manifestation of IKAROS haploinsufficiency.

引用

页数：5

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